1. Field of the Invention
In a complex industrial world, the human population is subjected to a continuously changing environment. Many of the physical and chemical components of the environment can affect the accuracy of replication of the genome of host cells. There is substantial concern with mutagenic agents in the environment, due to the established relationship between mutagenesis and carcinogenesis.
In many situations, it would be desirable to have a rapid simple screening procedure which would provide for a mutagenicity index. Such in index would allow for a comparison between various compounds as to their ability to cause lesions in a DNA sequence. In this manner, one could screen a large number of compounds and obtain a value for the mutagenic capability, which could serve as a characteristic of any physical or chemical component of the environment which might induce lesions.
Any system which is employed must take into consideration background values, resulting from spontaneous mutations or mutations which might result from complex interactions of the component of interest with the medium or other factor involving mutagenesis. Therefore, it is not sufficient that one has a system which allows for detection of DNA lesions, but rather one must show that the lesions which can be detected are a specific characteristic of the component being tested. Furthermore, it is desirable, if not necessary, that the agent be tested under conditions as closely tracking the naturally-occurring conditions, as possible.
2. Brief Description of the Relevant Literature
Calos et al., Proc. Natl. Acad. Sci. USA (1983) 80:3015-3019 describes the use of a lacI gene of E. coli to score mutation in mammalian cells. Lebkowski et al., Molec. Cell. Biol. (1984) 4:1951-1960 describes the uses of papovavirus-based shuttle vectors containing the bacterial lacI gene to demonstrate mutation frequency in transfected COS7 and CV-1 simian cells, NIH 3T3, 3T6, L and C127 mouse cells and human 293 and HeLa cells. Razzaque et al. Proc. Natl. Acad. Sci. USA (1983) 80:3010-3014, report employing galK as a marker for detecting lesions resulting from transfection into SV40 permissive cells. Yates et al. Proc. Natl. Acad. Sci USA (1984) 81:3806-3810 reports a replication system from EBV which provides episomal maintenance in a human EBV transformed cell. See also, Yates et al. Nature (1985) 313:812-815 which references are incorporated herein by reference.